In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

Shh regulates M2 microglial polarization and fibrotic scar formation after ischemic stroke.

BACKGROUND: Fibrotic scar formation is a critical pathological change impacting tissue reconstruction and functional recovery after ischemic stroke. The regulatory mechanisms behind fibrotic scarring in the central nervous system (CNS) remain largely unknown. While macrophages are known to play a role in fibrotic scar formation in peripheral tissues, the involvement of microglia, the resident immune cells of the CNS, in CNS fibrosis requires further exploration. The Sonic Hedgehog (Shh) signaling pathway, pivotal in embryonic development and tissue regeneration, is also crucial in modulating fibrosis in peripheral tissues. However, the impact and regulatory mechanisms of Shh on fibrotic scar formation post-ischemic stroke have not been thoroughly investigated. METHODS: This study explores whether Shh can regulate fibrotic scar formation post-ischemic stroke and its underlying mechanisms through in vivo and in vitro manipulation of Shh expression. RESULTS: Our results showed that Shh expression was upregulated in the serum of acute ischemic stroke patients, as well as in the serum, CSF, and ischemic regions of MCAO/R mice. Moreover, the upregulation of Shh expression was positively correlated with fibrotic scar formation and M2 microglial polarization. Shh knockdown inhibited fibrotic scar formation and M2 microglial polarization while aggravating neurological deficits in MCAO/R mice. In vitro, adenoviral knockdown or Smoothened Agonist (SAG) activation of Shh expression in BV2 cells following OGD/R regulated their polarization and influenced the expression of TGFß1 and PDGFA, subsequently affecting fibroblast activation. CONCLUSION: These results suggest that Shh regulates M2 microglial polarization and fibrotic scar formation after cerebral ischemia.

Accurately identifying incident cases of venous thromboembolism in the electronic health record: Performance of a novel phenotyping algorithm.

BACKGROUND: Accurate identification of incident venous thromboembolism (VTE) for quality improvement and health services research is challenging. The purpose of this study was to evaluate the performance of a novel incident VTE phenotyping algorithm defined using standard terminologies, requiring three key indicators documented in the electronic health record (EHR): VTE diagnostic code, VTE-related imaging procedure code, and anticoagulant medication code. METHODS: Retrospective chart reviews were conducted to assess the performance of the algorithm using a random sample of phenotype(+) and phenotype(-) diagnostic encounters from primary care practices and acute care sites affiliated with five hospitals across a large integrated care delivery system in Massachusetts. The performance of the algorithm was evaluated by calculating the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity, using the phenotype(+) and phenotype(-) diagnostic encounters sample and target population data. RESULTS: Based on gold-standard manual chart review, the algorithm had a PPV of 95.2 % (95 % CI: 93.1-96.8 %), NPV of 97.1 % (95 % CI: 95.3-98.4 %), sensitivity of 91.7 % (95 % CI: 90.8-92.6 %), and specificity of 98.4 % (95 % CI: 98.1-98.6 %). The algorithm systematically misclassified a low number of specific types of encounters, highlighting potential areas for improvement. CONCLUSIONS: This novel phenotyping algorithm offers an accurate approach for identifying incident VTE in general populations using EHR data and standard terminologies, and accurately identifies the specific encounter and date of diagnosis of the incident VTE. This approach can be used for measurement of incident VTE to drive quality improvement, research to expand the evidence, and development of quality metrics and clinical decision support to improve the diagnostic process.

Generative Large Language Models in Electronic Health Records for Patient Care Since 2023: A Systematic Review.

Background: Generative Large language models (LLMs) represent a significant advancement in natural language processing, achieving state-of-the-art performance across various tasks. However, their application in clinical settings using real electronic health records (EHRs) is still rare and presents numerous challenges. Objective: This study aims to systematically review the use of generative LLMs, and the effectiveness of relevant techniques in patient care-related topics involving EHRs, summarize the challenges faced, and suggest future directions. Methods: A Boolean search for peer-reviewed articles was conducted on May 19th, 2024 using PubMed and Web of Science to include research articles published since 2023, which was one month after the release of ChatGPT. The search results were deduplicated. Multiple reviewers, including biomedical informaticians, computer scientists, and a physician, screened the publications for eligibility and conducted data extraction. Only studies utilizing generative LLMs to analyze real EHR data were included. We summarized the use of prompt engineering, fine-tuning, multimodal EHR data, and evaluation matrices. Additionally, we identified current challenges in applying LLMs in clinical settings as reported by the included studies and proposed future directions. Results: The initial search identified 6,328 unique studies, with 76 studies included after eligibility screening. Of these, 67 studies (88.2%) employed zero-shot prompting, five of them reported 100% accuracy on five specific clinical tasks. Nine studies used advanced prompting strategies; four tested these strategies experimentally, finding that prompt engineering improved performance, with one study noting a non-linear relationship between the number of examples in a prompt and performance improvement. Eight studies explored fine-tuning generative LLMs, all reported performance improvements on specific tasks, but three of them noted potential performance degradation after fine-tuning on certain tasks. Only two studies utilized multimodal data, which improved LLM-based decision-making and enabled accurate rare disease diagnosis and prognosis. The studies employed 55 different evaluation metrics for 22 purposes, such as correctness, completeness, and conciseness. Two studies investigated LLM bias, with one detecting no bias and the other finding that male patients received more appropriate clinical decision-making suggestions. Six studies identified hallucinations, such as fabricating patient names in structured thyroid ultrasound reports. Additional challenges included but were not limited to the impersonal tone of LLM consultations, which made patients uncomfortable, and the difficulty patients had in understanding LLM responses. Conclusion: Our review indicates that few studies have employed advanced computational techniques to enhance LLM performance. The diverse evaluation metrics used highlight the need for standardization. LLMs currently cannot replace physicians due to challenges such as bias, hallucinations, and impersonal responses.

The siEGFR nanoplexes for the enhanced brain glioma treatment: Endoplasmic reticulum biomimetic strategy to induce homing effect and non-degradable intracellular transport.

The epidermal growth factor receptor (EGFR) plays a pivotal role in tumor progression and is an essential therapeutic target for treating malignant gliomas. Small interfering RNA (siRNA) has the potential to selectively degrade EGFR mRNA, yet its clinical utilization is impeded by various challenges, such as inefficient targeting and limited escape from lysosomes. Our research introduces polyethylene glycol (PEG) and endoplasmic reticulum membrane-coated siEGFR nanoplexes (PEhCv/siEGFR NPs) as an innovative approach to brain glioma therapy by overcoming several obstacles: 1) Tumor-derived endoplasmic reticulum membrane modifications provide a homing effect, facilitating targeted accumulation and cellular uptake; 2) Endoplasmic reticulum membrane proteins mediate a non-degradable "endosome-Golgi-endoplasmic reticulum" transport pathway, circumventing lysosomal degradation. These nanoplexes demonstrated significantly enhanced siEGFR gene silencing in both in vitro and in vivo U87 glioma models. The findings of this study pave the way for the advanced design and effective application of nucleic acid-based therapeutic nanocarriers.

Rapid toxicity characterization of Aconitum herbal medicines using perfusion nano-electrospray ionization mass spectrometry.

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Cellular indexing of transcriptomes and epitopes (CITE-Seq) in hidradenitis suppurativa identifies dysregulated cell types in peripheral blood and facilitates diagnosis via machine learning.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and scarring, predominantly affecting intertriginous regions. This study aimed to utilize single cell RNA and cell-surface protein sequencing (CITE-Seq) to delineate the immune composition of circulating cells in Hidradenitis suppurativa (HS) peripheral blood compared to healthy controls. CITE-Seq was used to analyze the gene and protein expression profiles of peripheral blood mononuclear cells (PBMCs) from 9 HS and 29 healthy controls. The study identified significant differences cell composition between HS patients and healthy controls, including increased proportions of CD14+ and CD16+ monocytes, cDC2, plasmablasts, and proliferating CD4+ T cells in HS patients. Differential expression analysis revealed upregulation of inflammatory markers such as TNF, IL1B, and NF-κB in monocytes, as well as chemokines and cell adhesion molecules involved in immune cell recruitment and tissue infiltration. Pathway enrichment analysis highlighted the involvement of IL-17, IL-26 and TNF signaling pathways in HS pathogenesis. Machine learning identified key markers for diagnostics and therapeutic development. The findings also support the potential for machine learning models to aid in the diagnosis of HS based on immune cell markers. These insights may inform future therapeutic strategies targeting specific immune pathways in HS.

Risk factor differences in five-year progression of Intracranial artery stenosis and cerebral small vessel disease in general population.

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.

Sexual and Gender-Diverse Individuals Face More Health Challenges during COVID-19: A Large-Scale Social Media Analysis with Natural Language Processing.

Background: The COVID-19 pandemic has caused a disproportionate impact on the sexual and gender-diverse (SGD) community. Compared with non-SGD populations, their social relations and health status are more vulnerable, whereas public health data regarding SGD are scarce. Methods: To analyze the concerns and health status of SGD individuals, this cohort study leveraged 471,371,477 tweets from 251,455 SGD and 22,644,411 non-SGD users, spanning from 2020 February 1 to 2022 April 30. The outcome measures comprised the distribution and dynamics of COVID-related topics, attitudes toward vaccines, and the prevalence of symptoms. Results: Topic analysis revealed that SGD users engaged more frequently in discussions related to "friends and family" (20.5% vs. 13.1%, P < 0.001) and "wear masks" (10.1% vs. 8.3%, P < 0.001) compared to non-SGD users. Additionally, SGD users exhibited a marked higher proportion of positive sentiment in tweets about vaccines, including Moderna, Pfizer, AstraZeneca, and Johnson & Johnson. Among 102,464 users who self-reported COVID-19 diagnoses, SGD users disclosed significantly higher frequencies of mentioning 61 out of 69 COVID-related symptoms than non-SGD users, encompassing both physical and mental health challenges. Conclusion: The results provide insights into an understanding of the unique needs and experiences of the SGD community during the pandemic, emphasizing the value of social media data in epidemiological and public health research.

Bioactive Nb2C MXene-Functionalized Hydrogel with Microenvironment Remodeling and Enhanced Neurogenesis to Promote Skeletal Muscle Regeneration and Functional Restoration.

The complete structure-functional repair of volumetric muscle loss (VML) remains a giant challenge and biomedical hydrogels to remodel microenvironment and enhance neurogenesis have appeared to be a promising direction. However, the current hydrogels for VML repair hardly achieve these two goals simultaneously due to their insufficient functionality and the challenge in high-cost of bioactive factors. In this study, a facile strategy using Nb2C MXene-functionalized hydrogel (OPTN) as a bioactive scaffold is proposed to promote VML repair with skeletal muscle regeneration and functional restoration. In vitro experiments show that OPTN scaffold can effectively scavenge reactive oxygen species (ROS), guide macrophages polarization toward M2 phenotype, and resist bacterial infection, providing a favorable microenvironment for myoblasts proliferation as well as the endothelial cells proliferation, migration, and tube formation. More importantly, OPTN scaffold with electroactive feature remarkably boosts myoblasts differentiation and mesenchymal stem cells neural differentiation. Animal experiments further confirm that OPTN scaffold can achieve a prominent structure-functional VML repair by attenuating ROS levels, alleviating inflammation, reducing fibrosis, and facilitating angiogenesis, newborn myotube formation, and neurogenesis. Collectively, this study provides a highly promising and effective strategy for the structure-functional VML repair through designing bioactive multifunctional hydrogel with microenvironment remodeling and enhanced neurogenesis.

Mapping Spatial Strain Distribution and Its Effects on Optoelectronic Properties in Wrinkled Perovskite Films.

Organic-inorganic halide perovskite films, fabricated by using the antisolvent method, have garnered intense attention for their application in high-efficiency and stable solar cells. These films characteristically develop periodic wrinkled microstructures. Previous research has indicated that macroscopic residual strain significantly influences the optoelectronic behaviors of these films. However, the detailed interplay between the wrinkled morphology, strain distribution, and local photophysical properties at the micro- and nanoscale has not been fully elucidated. Here, we explore the microscopic morphology-strain-property relationship within wrinkled perovskite films employing correlative micro-optical and nanoelectrical microscopy techniques. Microphotoluminescence (PL) mapping supplemented by in situ strain PL measurements identifies a heterogeneous spatial strain distribution across the microstructural hills and valleys. Additionally, light-intensity-dependent photoconductive atomic force microscopy reveals that valleys experiencing less compressive strain exhibit a lower conductivity and a higher propensity for ion migration. The findings underscore the potential of targeted strain engineering to optimize the performance and longevity of perovskite solar cells.

Gastrointestinal tract organoids as novel tools in drug discovery.

Organoids, characterized by their high physiological attributes, effectively preserve the genetic characteristics, physiological structure, and function of the simulated organs. Since the inception of small intestine organoids, other organoids for organs including the liver, lungs, stomach, and pancreas have subsequently been developed. However, a comprehensive summary and discussion of research findings on gastrointestinal tract (GIT) organoids as disease models and drug screening platforms is currently lacking. Herein, in this review, we address diseases related to GIT organoid simulation and highlight the notable advancements that have been made in drug screening and pharmacokinetics, as well as in disease research and treatment using GIT organoids. Organoids of GIT diseases, including inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and Helicobacter pylori infection, have been successfully constructed. These models have facilitated the study of the mechanisms and effects of various drugs, such as metformin, Schisandrin C, and prednisolone, in these diseases. Furthermore, GIT organoids have been used to investigate viruses that elicit GIT reactions, including Norovirus, SARS-CoV-2, and rotavirus. Previous studies by using GIT organoids have shown that dasabuvir, gemcitabine, and imatinib possess the capability to inhibit viral replication. Notably, GIT organoids can mimic GIT responses to therapeutic drugs at the onset of disease. The GIT toxicities of compounds like gefitinib, doxorubicin, and sunset yellow have also been evaluated. Additionally, these organoids are instrumental for the study of immune regulation, post-radiation intestinal epithelial repair, treatment for cystic fibrosis and diabetes, the development of novel drug delivery systems, and research into the GIT microbiome. The recent use of conditioned media as a culture method for replacing recombinant hepatocyte growth factor has significantly reduced the cost associated with human GIT organoid culture. This advancement paves the way for large-scale culture and compound screening of GIT organoids. Despite the ongoing challenges in GIT organoid development (e.g., their inability to exist in pairs, limited cell types, and singular drug exposure mode), these organoids hold considerable potential for drug screening. The use of GIT organoids in this context holds great promises to enhance the precision of medical treatments for patients living with GIT diseases.

Urolithin a Improves Motor Dysfunction Induced by Copper Exposure in SOD1G93A Transgenic Mice Via Activation of Mitophagy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease pathologically characterized by selective degeneration of motor neurons resulting in a catastrophic loss of motor function. The present study aimed to investigate the effect of copper (Cu) exposure on progression of ALS and explore the therapeutic effect and mechanism of Urolithin A (UA) on ALS. 0.13 PPM copper chloride drinking water was administrated in SOD1G93A transgenic mice at 6 weeks, UA at a dosage of 50 mg/kg/day was given for 6 weeks after a 7-week Cu exposure. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl and Immunohistochemistry Staining. Proteomics analysis, Western blotting and ELISA were conducted to detect protein expression. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. Cu-exposure worsened motor function, promoted muscle fibrosis, loss of motor neurons, and astrocyte and microglial activation. It also induced abnormal changes in mitochondria-related biological processes, leading to a significant reduction in ATP levels and an increase in MDA levels. Upregulation of P62 and downregulation of Parkin, PINK1, and LAMP1 were revealed in SOD1G93A mice with Cu exposure. Administration of UA activated mitophagy, modulated mitochondria dysfunction, reduced neuroinflammation, and improved gastrocnemius muscle atrophy and motor dysfunction in SOD1G93A mice with Cu exposure. Mitophagy plays critical role in ALS exacerbated by Cu exposure. UA administration may be a promising treatment strategy for ALS.

Metabolic evolution and bottleneck insights into simultaneous autotroph-heterotroph anammox system for real municipal wastewater nitrogen removal.

When biological nitrogen removal (BNR) systems shifted from treating simulated wastewater to real wastewater, a microbial succession occurred, often resulting in a decline in efficacy. Notably, despite their high nitrogen removal efficiency for real wastewater, anammox coupled systems operating without or with minimal carbon sources also exhibited a certain degree of performance reduction. The underlying reasons and metabolic shifts within these systems remained elusive. In this study, the simultaneous autotrophic/heterotrophic anammox system demonstrated remarkable metabolic resilience upon exposure to real municipal wastewater, achieving a nitrogen removal efficiency (NRE) of 82.83 ± 2.29 %. This resilience was attributed to the successful microbial succession and the complementary metabolic functions of heterotrophic microorganisms, which fostered a resilient microbial community. The system's ability to harness multiple electron sources, including NADH oxidation, the TCA cycle, and organics metabolism, allowed it to establish a stable and efficient electron transfer chain, ensuring effective nitrogen removal. Despite the denitrification channel's nitrite supply capability, the analysis of the interspecies correlation network revealed that the synergistic metabolism between AOB and AnAOB was not fully restored, resulting in selective functional bacterial and genetic interactions and the system's PN/A performance declined. Additionally, the enhanced electron affinity of PD increased interconversion of NO3--N and NO2--N, limiting the efficient utilization of electrons and thereby constraining nitrogen removal performance. This study elucidated the metabolic mechanism of nitrogen removal limitations in anammox-based systems treating real municipal wastewater, enhancing our understanding of the metabolic functions and electron transfer within the symbiotic bacterial community.

Non-linear relationship between TyG index and the risk of prediabetes in young people: a 5-year retrospective cohort study in Chinese young adults.

Objective: Given the limited evidence on the relationship between the triglyceride-glucose (TyG) index and the risk of prediabetes among young adults, our study aimed to investigate the potential impact of the TyG index on the future development of prediabetes in young individuals. Methods: This retrospective cohort study included 125,327 healthy adults aged 20 to 45 years. We utilized Cox proportional hazards regression models, combined with cubic spline functions and smooth curve fitting, to assess the relationship between baseline TyG index and the risk of prediabetes among young adults, exploring its non-linear association. A series of sensitivity analyses and subgroup analyses were conducted to ensure the robustness of our findings. Results: After adjusting for covariates, the study found a positive correlation between the TyG index and the risk of prediabetes (HR=1.81, 95%CI: 1.54-2.13, p<0.0001). The risk of prediabetes increased progressively across quartiles of the TyG index (Q1 to Q4), with Q4 showing a significantly higher risk compared to Q1 (adjusted HR=2.33, 95% CI=1.72-3.16). Moreover, a non-linear relationship was identified between the TyG index and the risk of prediabetes, with an inflection point at 9.39. To the left of the inflection point, the HR was 2.04 (95% CI: 1.69 to 2.46), while to the right, the HR was 0.89 (95% CI: 0.48 to 1.65). Conclusion: Our study reveals a non-linear relationship and a saturation effect between the TyG index and the development of prediabetes among young individuals in China, with an inflection point at 9.39. Understanding this non-linear relationship can assist clinicians in identifying young individuals at high risk and implementing targeted interventions to reduce their risk of progressing to diabetes.

Arginine on immune function and post-operative obstructions in colorectal cancer patients: a meta-analysis.

BACKGROUND: The aim of this study is to investigate the impact of arginine on immune function and postoperative complications in colorectal cancer (CRC) patients. METHODS: We conducted a comprehensive search to identify eligible RCTs in various databases, such as PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Medicine Information System (VIP), and Chinese Biomedical Database (CBM). This study aimed to examine IgA, IgG, and IgM levels as well as CD4+ and CD8+ counts as well as the CD4+/CD8+ ratio. Anastomotic leaking, length of stay (LOS), and surgical site infection (SSI) were included as secondary outcomes. Stata (StataCorp, version 14.0) was utilized for data analysis. To ensure the results were reliable, we used meta-regression, sensitivity analysis, and publication bias analysis. RESULTS: A total of 24 publications (including 1883 patients) out of 681 that were retrieved fulfilled the inclusion criteria. The arginine group showed notable improvements in humoral immunity, with gains in IgA (SMD=0.45, 95% CI: 0.30-0.60), IgG (SMD=0.80, 95% CI: 0.64-0.96), and IgM (SMD=0.66, 95% CI: 0.39-0.93). With regards to cellular immunity, the arginine group exhibited a substantial increase in the CD4+ T cell count (SMD = 1.03, 95% CI: 0.67-1.38) compared to the control group. However, the CD4+/CD8+ ratio decreased significantly (SMD=1.37, 95% CI: 0.88-1.86) in the same arginine group, indicating a change in the balance between these two cell types. Additionally, the CD8+ T cell count showed a notable decrease (SMD=-0.70, 95% CI: -1.09 to -0.32) in the arginine group when compared to the control group. Anastomotic leakage was also considerably lower in the arginine group (SMD=-0.05, 95% CI: -0.08 to -0.02), the rate of SSIs was lower (RR = -0.02, 95% CI: -0.05-0), and the length of time patients spent in the hospital was shorter (SMD=-0.15, 95% CI: -0.38 to -0.08). CONCLUSIONS: After radiation treatment for CRC, arginine improves immune function and decreases the risk of infection problems. TRIAL REGISTRATION: Registration with PROSPERO for this meta-analysis is number CRD42024520509.

Long-term expanded hepatic progenitor cells ameliorate D-GalN/LPS-induced acute liver failure through repolarizing M1 macrophage to M2-Like phenotype via activation of the IL-10/JAK2/STAT3 signaling pathway.

Acute liver failure (ALF) is a devastating liver disease characterized by the rapid deterioration of hepatocytes, which causes a series of clinical complications, including hepatic dysfunction, coagulopathy, encephalopathy, and multiorgan failure. Cell-based therapy is a promising alternative as it can bridge patients until their livers regenerate, releasing immunomodulatory molecules to suppress inflammation. This study reports an iPSCs-derived long-term expanded hepatic progenitor cell (LTHepPCs), which can differentiate into hepatocyte-like cells (HLCs) in vivo. When introduced into drug-induced ALF models, LTHepPCs mitigate liver damage by modulating the local immune microenvironment. This is achieved by shifting macrophages/Kupffer cells towards an anti-inflammatory state, resulting in a decrease in the expression of inflammatory cytokines such as TNF-a, IL-1ß, and IL-8, and an increase in the expression of anti-inflammatory cytokines such as IL-10 and ARG-1. In vitro co-culturing of THP-1 or mBMDMs with LTHepPCs suggested that LTHepPCs could activate the anti-inflammatory state of macrophages/Kupffer cells via the IL-10/JAK2/STAT3 signaling pathway. Therefore, LTHepPC transplantation is a promising therapy for ALF patients.

Effects of aerobic exercise-based pulmonary rehabilitation on quality of life in pediatric asthma: A systematic review and meta-analysis.

BACKGROUND: Pediatric asthma poses a significant global health burden, impacting the well-being and daily lives of affected children. Aerobic exercise-based pulmonary rehabilitation emerges as a promising intervention to address the multifaceted challenges faced by pediatric asthma patients. OBJECTIVES: The purpose of this systematic review and meta-analysis was to comprehensively evaluate the effects of aerobic exercise-based pulmonary rehabilitation on pulmonary function and quality of life in pediatric asthma patients. METHODS: Randomized controlled trials (RCTs) involving pediatric participants (5-18 years) were included. Aerobic exercise program-based pulmonary rehabilitation interventions were assessed for their impact on actual and percentage predicted values of lung volumes and flow rates such as forced vital capacity (FVC), maximum mid-expiratory flow (FEF25-75), peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), FEV1/FVC, and on quality of life (QoL) measures. A systematic search of databases, hand-searching, and consultation with experts identified relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines guided study selection, data extraction, and quality assessment. RESULTS: The systematic review included 20 studies with diverse exercise interventions and outcomes. The meta-analysis using fixed-effects model showed that there was a significant improvement in FVC (% predicted) [SMD= 0.30, 95 %CI: 0.13, 0.48] and FEF25-75 (% predicted) [SMD= 0.31, 95 %CI: 0.03, 0.58] in the experimental group compared with the control group. Furthermore, using a random-effects model involving 12 studies, significant increases in the QoL [SMD= 0.70, 95 %CI: 0.14, 1.26] were found in the exercise group. Due to inter-study heterogeneity, additional analyses were conducted. Publication bias analysis indicated robustness, with no significant asymmetry in funnel plots. CONCLUSION: Aerobic exercise-based pulmonary rehabilitation significantly enhances pulmonary function and quality of life in pediatric asthma patients. The findings, supported by improvements in FVC and FEF25-75, demonstrate the efficacy of these interventions. Quality of life measures also showed notable improvements. Despite inter-study heterogeneity, the results are robust, suggesting that aerobic exercise should be considered a valuable non-pharmacological strategy in managing pediatric asthma.

Methylparaben changes the community composition, structure, and assembly processes of free-living bacteria, phytoplankton, and zooplankton.

Parabens are common contaminants in river and lake environments. However, few studies have been conducted to determine the effects of parabens on bacteria, phytoplankton, and zooplankton communities in aquatic environments. In this study, the effect of methylparaben (MP) on the diversity and community structure of the aquatic plankton microbiome was investigated by incubating a microcosm with MP at 0.1, 1, 10, and 100 µg/L for 7 days. The results of the Simpson index showed that MP treatment altered the α-diversity of free-living bacteria (FL), phytoplankton, and zooplankton but had no significant effect on the α-diversity of particle-attached bacteria (PA). Further, the relative abundances of the sensitive bacteria Chitinophaga and Vibrionimonas declined after MP addition. Moreover, the relative abundances of Desmodesmus sp. HSJ717 and Scenedesmus armatus, of the phylum Chlorophyta, were significantly lower in the MP treatment group than in the control group. In addition, the relative abundance of Stoeckeria sp. SSMS0806, of the Dinophyta phylum, was higher than that in the control group. MP addition also increased the relative abundance of Arthropoda but decreased the relative abundance of Rotifera and Ciliophora. The ß-diversity analysis showed that FL and phytoplankton communities were clustered separately after treatment with different MP concentrations. MP addition changed community assembly mechanisms in the microcosm, including increasing the stochastic processes for FL and the deterministic processes for PA and phytoplankton. Structural equation modeling analysis showed a significant negative relationship between bacteria richness and phytoplankton richness, and a significant positive relationship between phytoplankton (richness and community composition) and zooplankton. Overall, this study emphasizes that MP, at environmental concentrations, can change the diversity and structure of plankton microbial communities, which might have a negative effect on ecological systems.